Zostavax vaccination-induced changes in the T cell receptor repertoire to varicella zoster virus

Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood is able to escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-specific CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV. While all individuals had a small number of dominant T cell clones, the breadth of the VZV-specific repertoire differed markedly among different individuals. A genetic influence was seen for the sharing of individual TCR sequences from antigen-specific cells, but not for repertoire richness or the selection of clonal dominance. VZV vaccination favored the expansion of infrequent VZV-specific TCRs including those from naïve T cells while leaving dominant T cell clones mostly unaffected.

• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
  • Cohort
• Total number of consented subjects: 9
• Subject Sample Telemetry Report (SSTR)

• PubMed

Inclusion:

• Healthy individuals older than 50 years

Exclusion:

• History of shingles within 5 years of enrollment
• Prior vaccination with Zostavax vaccine for prevention of shingles
• History of severe allergic reactions to vaccine components, including gelatin and neomycin
• Life-threatening reactions to previous vaccinations
• Adults weighing less than 110 pounds
• Active systemic or serious concurrent illness, including febrile illness on the day of enrollment/vaccination
• History of immunodeficiency disorder
• Chronic HIV, Hepatitis B or Hepatitis C infection
• Known or suspected impairment of immunologic function, including, but not limited to clinically significant liver disease, diabetes mellitus treated with insulin, moderate to severe renal disease or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• Recent or current use of immunosuppressive medication, or anticipated use during study period, including systemic corticosteroids (corticosteroid nasal sprays, inhaled steroids and topical steroids are permissible).
• Blood pressure >150 systolic or >95 diastolic at Visit 1 12. History of chemotherapy treatment for cancer. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer with recurrence in the past year and any hematologic cancer such as leukemia or lymphoma), which in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol. Prostate cancer may be acceptable if no metastases and not undergoing treatment with immunosuppressive medications.
• Autoimmune disease, including rheumatoid arthritis, treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel, which in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol (thyroid disease may be acceptable).
• History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
• Use of anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except aspirin up to 325 mg. daily), Plavix or Aggrenox which may, in the opinion of the investigator, jeopardize volunteer safety or compliance with the protocol.
• Receipt of blood or blood products within 6 months prior to enrollment and during the study period
• Use of antiviral medications within 24 hrs. prior to enrollment, and for the 14 days following study vaccination.
• Inactivated vaccine within 14 days prior to enrollment and during study period
• Live, attenuated vaccine within 60 days prior to enrollment and during study period
• Pregnant or lactating woman, planning to become pregnant (pregnancy should be avoided for 3 months following administration of Zostavax vaccine).
• Use of investigational agents within 30 days prior to enrollment and during study period
• Donation of a unit of blood within 6 weeks prior to enrollment and during study period
• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol
• Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.

Study recruitment and vaccination with Zostavax was performed between June 2010 and December 2014.

• Primary Phenotype: Herpes Zoster
• Receptors, Antigen, T-Cell, alpha-beta
• Vaccination

• TRB

• Principal Investigator
  • Jorg J. Goronzy, MD PhD. Stanford University, Stanford, CA, USA.
• Funding Sources
  • U19-AI090019. National Institutes of Health, Bethesda, MD, USA.